The drug abuse problem in general and the widespread use of marihuana in particular has focused attention on the chemistry and pharmacology of this plant (Cannabis Sativa). Although rapid advances have been made in the chemistry of this class of compounds some aspects are not very well understood. The basic problem stems from the fact that the thermodynamically less stable isomer delta 9-tetrahydrocannabinol (THC) is the main constituent of marihuana compared to the more stable isomer delta 8-THC. This has posed many synthetic problems as during chemical reactions mostly the more stable derivatives of delta 8-THC are formed. As a result of the work carried out to date on this grant, we have discovered a simple one-step synthesis of delta 9-THC, the active constituent of marihuana and found experimental conditions for preventing the isomerization of delta 9- to delta 8-THC. The work proposed in this application will allow us to further develop methods and the new process for the preparation of other delta 9-THC analogues and derivatives including metabolites which are now urgently required for advanced pharmacological and toxicity studies. The equilibrium studies between cis and trans THCs have already provided a better understanding of the thermodynamic stability and thus of the chemistry of various cannabinoids. Furthermore, our studies have revealed new structure-activity requirements in THCs. The present study on the chemistry and SAR of cannabis constituents will help in combatting the drug abuse problem which has had profound effects on our present day society.